314 research outputs found
Analysis of Diffusion of Ras2 in Saccharomyces cerevisiae Using Fluorescence Recovery after Photobleaching
Binding, lateral diffusion and exchange are fundamental dynamic processes
involved in protein association with cellular membranes. In this study, we
developed numerical simulations of lateral diffusion and exchange of
fluorophores in membranes with arbitrary bleach geometry and exchange of the
membrane localized fluorophore with the cytosol during Fluorescence Recovery
after Photobleaching (FRAP) experiments. The model simulations were used to
design FRAP experiments with varying bleach region sizes on plasma-membrane
localized wild type GFP-Ras2 with a dual lipid anchor and mutant GFP-Ras2C318S
with a single lipid anchor in live yeast cells to investigate diffusional
mobility and the presence of any exchange processes operating in the time scale
of our experiments. Model parameters estimated using data from FRAP experiments
with a 1 micron x 1 micron bleach region-of-interest (ROI) and a 0.5 micron x
0.5 micron bleach ROI showed that GFP-Ras2, single or dual lipid modified,
diffuses as single species with no evidence of exchange with a cytoplasmic
pool. This is the first report of Ras2 mobility in yeast plasma membrane. The
methods developed in this study are generally applicable for studying diffusion
and exchange of membrane associated fluorophores using FRAP on commercial
confocal laser scanning microscopes.Comment: Accepted for publication in Physical Biology (2010). 28 pages, 7
figures, 3 table
Associations Between Nutrient Intake and Corresponding Nutritional Biomarker Levels in Blood in a Memory Clinic Cohort:The NUDAD Project
Diet is a promising intervention target to prevent or slow Alzheimer's disease (AD). Early (predementia) stages of AD offer a unique opportunity for dietary interventions. Nutritional assessment methods to estimate nutrient intake have, however, not been validated in clinical populations. Hence, we assessed the association between nutrient intake assessed by food frequency questionnaire (FFQ) and nutrient status measured by nutritional biomarkers in blood in a clinical sample of controls, mild cognitive impairment (MCI), and patients with AD
Immunohistochemical localization of collagen types I and VI in human skin wounds
A total of 74 human skin wounds were investigated and collagen types I and VI were localized in the wound area by immunohistochemistry. Collagen type I appeared in the form of ramifying string-like structures after approximately 5–6 days, but positive reactions in the form of a spot-like staining around isolated fibroblasts also occurred in a skin wound aged 4 days. Collagen VI was detectable after a post-infliction interval of at least 3 days showing a strongly positive reacting network associated with fibroblasts in the wound area. Both collagens appeared almost constantly after a wound age of 6–7 clays and could also be found in wounds aged a few months. Therefore, although a positive reaction for collagen type I in the form of string-like and ramifying structures around wound fibroblasts indicates a wound age of at least 5–6 days, a spot-like positive staining for collagen type I cannot exclude a wound age of at least 4 days. A positive staining for collagen type VI represents a post-infliction time of 3 days or more. The almost constant appearance of these collagen types suggests that negative results in a sufficient number of specimens indicate a wound age of less than 6–7 days, but cannot completely exclude longer post-infliction intervals. Since collagen type I and VI are also found in the granulation/scar tissue of lesions with advanced wound age, the immunohistochemical analysis of these proteins provides no further information for an age determination of older skin wounds
Pan-STARRS1 Discovery of Two Ultra-Luminous Supernovae at z ~ 0.9
We present the discovery of two ultra-luminous supernovae (SNe) at z ~ 0.9
with the Pan-STARRS1 Medium-Deep Survey. These SNe, PS1-10ky and PS1-10awh, are
amongst the most luminous SNe ever discovered, comparable to the unusual
transients SN 2005ap and SCP 06F6. Like SN 2005ap and SCP 06F6, they show
characteristic high luminosities (M_bol ~ -22.5 mag), blue spectra with a few
broad absorption lines, and no evidence for H or He. We have constructed a full
multi-color light curve sensitive to the peak of the spectral energy
distribution in the rest-frame ultraviolet, and we have obtained time-series
spectroscopy for these SNe. Given the similarities between the SNe, we combine
their light curves to estimate a total radiated energy over the course of
explosion of (0.9-1.4) x 10^51 erg. We find photospheric velocities of
12,000-19,000 km/s with no evidence for deceleration measured across ~3
rest-frame weeks around light-curve peak, consistent with the expansion of an
optically-thick massive shell of material. We show that, consistent with
findings for other ultra-luminous SNe in this class, radioactive decay is not
sufficient to power PS1-10ky, and we discuss two plausible origins for these
events: the initial spin-down of a newborn magnetar in a core-collapse SN, or
SN shock breakout from the dense circumstellar wind surrounding a Wolf-Rayet
star.Comment: Re-Submitted to Ap
Mapping the multicausality of Alzheimer's disease through group model building
Alzheimer's disease (AD) is a complex, multicausal disorder involving several spatiotemporal scales and scientific domains. While many studies focus on specific parts of this system, the complexity of AD is rarely studied as a whole. In this work, we apply systems thinking to map out known causal mechanisms and risk factors ranging from intracellular to psychosocial scales in sporadic AD. We report on the first systemic causal loop diagram (CLD) for AD, which is the result of an interdisciplinary group model building (GMB) process. The GMB was based on the input of experts from multiple domains and all proposed mechanisms were supported by scientific literature. The CLD elucidates interaction and feedback mechanisms that contribute to cognitive decline from midlife onward as described by the experts. As an immediate outcome, we observed several non-trivial reinforcing feedback loops involving factors at multiple spatial scales, which are rarely considered within the same theoretical framework. We also observed high centrality for modifiable risk factors such as social relationships and physical activity, which suggests they may be promising leverage points for interventions. This illustrates how a CLD from an interdisciplinary GMB process may lead to novel insights into complex disorders. Furthermore, the CLD is the first step in the development of a computational model for simulating the effects of risk factors on AD.Neuro Imaging Researc
Cosmological Constraints from Galaxy Clusters in the 2500 square-degree SPT-SZ Survey
(abridged) We present cosmological constraints obtained from galaxy clusters
identified by their Sunyaev-Zel'dovich effect signature in the 2500 square
degree South Pole Telescope Sunyaev Zel'dovich survey. We consider the 377
cluster candidates identified at z>0.25 with a detection significance greater
than five, corresponding to the 95% purity threshold for the survey. We compute
constraints on cosmological models using the measured cluster abundance as a
function of mass and redshift. We include additional constraints from
multi-wavelength observations, including Chandra X-ray data for 82 clusters and
a weak lensing-based prior on the normalization of the mass-observable scaling
relations. Assuming a LCDM cosmology, where the species-summed neutrino mass
has the minimum allowed value (mnu = 0.06 eV) from neutrino oscillation
experiments, we combine the cluster data with a prior on H0 and find sigma_8 =
0.797+-0.031 and Omega_m = 0.289+-0.042, with the parameter combination
sigma_8(Omega_m/0.27)^0.3 = 0.784+-0.039. These results are in good agreement
with constraints from the CMB from SPT, WMAP, and Planck, as well as with
constraints from other cluster datasets. Adding mnu as a free parameter, we
find mnu = 0.14+-0.08 eV when combining the SPT cluster data with Planck CMB
data and BAO data, consistent with the minimum allowed value. Finally, we
consider a cosmology where mnu and N_eff are fixed to the LCDM values, but the
dark energy equation of state parameter w is free. Using the SPT cluster data
in combination with an H0 prior, we measure w = -1.28+-0.31, a constraint
consistent with the LCDM cosmological model and derived from the combination of
growth of structure and geometry. When combined with primarily geometrical
constraints from Planck CMB, H0, BAO and SNe, adding the SPT cluster data
improves the w constraint from the geometrical data alone by 14%, to w =
-1.023+-0.042
Isomeric recognition by ion/molecule reactions: The ionized phenol-cyclohexadienone case
Dietary patterns are related to cognitive functioning in elderly enriched with individuals at increased risk for Alzheimer's disease
PURPOSE: To investigate cross-sectional associations between dietary patterns and cognitive functioning in elderly free of dementia. METHODS: Data of 389 participants from the German DELCODE study (52% female, 69 ± 6 years, mean Mini Mental State Score 29 ± 1) were included. The sample was enriched with elderly at increased risk for Alzheimer's disease (AD) by including participants with subjective cognitive decline, mild cognitive impairment (MCI) and siblings of AD patients. Mediterranean and MIND diets were derived from 148 Food Frequency Questionnaire items, and data-driven patterns by principal component analysis (PCA) of 39 food groups. Associations between dietary patterns and five cognitive domain scores were analyzed with linear regression analyses adjusted for demographics (model 1), and additionally for energy intake, BMI, other lifestyle variables and APOe4-status (model 2). For PCA-derived dietary components, final model 3 included all other dietary components. RESULTS: In fully adjusted models, adherence to Mediterranean and MIND diet was associated with better memory. The 'alcoholic beverages' PCA component was positively associated with most cognitive domains. Exclusion of MCI subjects (n = 60) revealed that Mediterranean and MIND diet were also related to language functions; associations with the alcoholic beverages component were attenuated, but most remained significant. CONCLUSION: In line with data from elderly population samples, Mediterranean and MIND diet and some data-derived dietary patterns were related to memory and language function. Longitudinal data are needed to draw conclusions on the putative effect of nutrition on the rate of cognitive decline, and on the potential of dietary interventions in groups at increased risk for AD
- …